1. Field of the Invention
This invention relates to a method and apparatus for measuring a concentration of glucose in a living body. This invention particularly relates to a method and apparatus for non-invasively measuring the concentration of glucose in the aqueous humor in the anterior aqueous chamber of the eyeball.
2. Description of the Prior Art
The mean level of glucose in the blood varies for different persons and is an important index for determining whether drugs are to be or are not to be administered to diabetic patients.
The concentration of glucose in the blood has the characteristics such that it fluctuates markedly within a very short time in accordance with food intake, physical activity, a complication by another disease, or the like. Urgent dosage is often required due to a sharp increase in concentration of blood glucose.
Therefore, as for patients having such a disease, it is desired that the concentration of glucose in the blood can be monitored at as short intervals as possible. Ordinarily, monitoring of the concentration of glucose in the blood is carried out by lancing the finger of the patient in order to obtain a drop of blood, analyzing the drop of blood, and thereby measuring the concentration of glucose in the blood. Since the lancing of the finger is painful, it is difficult to compel the patients to undergo the measurement procedure many times per day.
Accordingly, recently, in lieu of the invasive measurements having the drawbacks described above, various non-invasive measuring methods, which are not accompanied by pain, have been proposed.
The non-invasive measuring methods are primarily based upon the findings in that the concentration of glucose in the aqueous humor, which fills the anterior aqueous chamber located between the cornea and the crystalline lens of the human eyeball, has strong correlation with the concentration of glucose in the blood, though the level of correlation varies for different persons. With the non-invasive measuring methods, the concentration of glucose in the aqueous humor is measured non-invasively.
For example, a glucose sensor system, wherein the angle of rotation of infrared radiation having impinged upon the aqueous humor is measured, and the concentration of glucose having relationship with the angle of rotation is thereby determined, is proposed in, for example, U.S. Pat. No. 3,958,560. Also, a technique for measuring stimulated Raman light from glucose is disclosed in, for example, PCT Japanese Publication No. 6(1994)-503245.
Further, a device for measuring the optical properties of light reflected from the crystalline lens of the eye is described in, for example, Japanese Unexamined Patent Publication No. 6(1994)-237898. Furthermore, a method of measuring the concentration of glucose in the aqueous humor is described in, for example, U.S. Pat. No. 5,433,197.
Also, in U.S. Pat. No. 5,835,215 a method of measuring a concentration of glucose in the aqueous humor by measuring an absorbance of the aqueous humor was proposed. In the proposed method, a signal light beam is irradiated to the eyeball, and the intensity of the signal light beam reflected from an interface between the anterior aqueous chamber and the crystalline lens of the eyeball is detected. In this manner, the absorbance of the aqueous humor is measured. Since the light beam, which is reflected from an interface between the cornea and the anterior aqueous chamber, is mixed as noise in the reflected signal light beam, in the proposed method, a heterodyne detection technique is utilized in order to eliminate the noise, and the concentration of glucose in the aqueous humor is detected accurately.
However, with the device described in Japanese Unexamined Patent Publication No. 6(1994)-237898, light reflected from the interface between the cornea and the aqueous humor cannot be eliminated, and information representing absorption at the cornea is detected together with the necessary information. Therefore, the accuracy, with which the concentration of glucose in the aqueous humor is determined, cannot be kept high.
Further, in Japanese Unexamined Patent Publication No. 6(1994)-237898, nothing is disclosed as to technical means to be used for measuring a minute change in absorbance. Therefore, the device described in Japanese Unexamined Patent Publication No. 6(1994)-237898 cannot be appropriately used in practice.
The technique proposed in U.S. Pat. No. 3,958,560 has the problems in that polarization occurs at respective interfaces in the eyeball, and it is not possible to separate only the polarized light due to the aqueous humor.
With the technique disclosed in PCT Japanese Publication No. 6(1994)-503245, in order for stimulated Raman light from glucose to be measured, a pump laser beam having a high intensity is introduced into the anterior aqueous chamber and in a direction normal to the vision line optical axis. Therefore, a practical measuring system cannot be constituted easily.
With the techniques for calculating the concentration of glucose in accordance with optical characteristic values of the aqueous humor, such as the absorbance or the refractive index, which are proposed in, for example, U.S. Pat No. 5,835,215 and PCT Japanese Publication No. 9(1997)-512722, such that adverse effects of the constituents (e.g., NaCl) other than glucose, which are contained in the aqueous humor, upon the optical characteristic values, such as the absorbance or the refractive index, may be eliminated, it is necessary for the measurement to be repeated by using at least five kinds of light beams having different wavelengths. Also, it is necessary for a correction of the optical characteristic values, such as the absorbance or the refractive index, to be made due to a temperature difference between a deep portion and a hallow portion in the anterior aqueous chamber, through which a light beam passes. Therefore, the measurement and the information processing cannot be kept simple.